Association between ADIPOQ G276T and C11377G polymorphisms and the risk of non‐alcoholic fatty liver disease: An updated meta‐analysis

Liu, Mengwei; Liu, Shan; Shang, Mengmeng; Liu, Xiuping; Wang, Yue; Li, Qian; Mambiya, Michael; Yang, Luping; Zhang, Qian; Zhang, Kaili; Nie, Fangfang; Zeng, Fanxin; Liu, Wanyang

doi:10.1002/mgg3.624

Cited by 11 publications

(7 citation statements)

References 31 publications

(35 reference statements)

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“…NAFLD is a multiple factor disease that is influenced by genetic variation, diet, age, sex, ethnicity, and lifestyle, along with conditions including obesity, insulin resistance, dyslipidemia, hypertension, diabetes mellitus, and metabolic syndrome ( Hamabe et al, 2011 ; Satapathy and Sanyal, 2015 ; Kalia and Gaglio, 2016 ; Tong and Guo, 2019 ; Zhang et al, 2019 ). Several studies have been conducted on the association between gene polymorphism and NAFLD ( Kong et al, 2017 ; Liu et al, 2019 ; Xu et al, 2019 ). Specifically, some studies have indicated that susceptibility genes may play an important role in the pathogenesis of NAFLD ( Sookoian and Pirola, 2011 ; Yang et al, 2011 ).…”

Section: Introductionmentioning

confidence: 99%

Associations Among Methylene Tetrahydrofolate Reductase rs1801133 C677T Gene Variant, Food Groups, and Non-alcoholic Fatty Liver Disease Risk in the Chinese Population

Hao

Xiang

et al. 2021

Front. Genet.

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ObjectivesTo investigate the associations among the methylene tetrahydrofolate reductase rs1801133 C677T gene variant, food groups, and the risk of non-alcoholic fatty liver disease in the Chinese population.MethodsA study of gene polymorphism was conducted using the polymerase chain reaction method. A total of 4,049 adults participated in the study, and all underwent physical examination and genotyping. Participants filled out a dietary questionnaire to enable us to assess the frequency and quantity of food consumption.ResultsThe important variables identified as risk factors of non-alcoholic fatty liver disease were age, smoking, sex, body mass index, hyperlipidemia, diabetes, and methylene tetrahydrofolate reductase genotype (T – allele carriers). The homocysteine content was higher in the non-alcoholic fatty liver disease group than in the control group, and was higher in the T- allele than C- allele carriers. The homocysteine content was the highest in the T- allele carriers. Additionally, certain food groups such as milk and beans were associated with a lower risk of non-alcoholic fatty liver disease. Food groups such as meat, were associated with a higher risk of non-alcoholic fatty liver disease. Fresh fruit and vegetables, salted and smoked foods, desserts, cereals, fish, and eggs were not associated with the risk of non-alcoholic fatty liver disease. However, the influence of salted and smoked foods on non-alcoholic fatty liver disease was different in the C-allele and T-allele carriers of methylene tetrahydrofolate reductase (CT + TT vs. CC, OR = 1.196, P = 0.041 for 1–4 times food per week, OR = 1.580, P = 0.004 for 5–7 times per week). Similarly, salted and smoked foods were also a risk factor for the development of non-alcoholic steatohepatitis in patients with non-alcoholic fatty liver disease.ConclusionThis study found that the T-allele of the C677T variant of methylene tetrahydrofolate reductase was a risk factor for non-alcoholic fatty liver disease among Chinese people. These results can likely aid the development of novel approaches for managing non-alcoholic fatty liver disease risk.

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Section: Introductionmentioning

confidence: 99%

Associations Among Methylene Tetrahydrofolate Reductase rs1801133 C677T Gene Variant, Food Groups, and Non-alcoholic Fatty Liver Disease Risk in the Chinese Population

Hao

Xiang

et al. 2021

Front. Genet.

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“…ADIPOQ (adiponectin) is an adipose-derived plasma protein that functions in hepatic lipoprotein-lipid metabolism [ 70 ]. Several pieces of evidence indicate that diverse polymorphisms in ADIPOQ may increase susceptibility to NAFLD [ 70 , 71 ]. One study reported that the ADIPOQ methylation rate in rats with NAFLD was higher than in control animals [ 72 ].…”

Section: Discussionmentioning

confidence: 99%

Target Deconvolution of Fenofibrate in Nonalcoholic Fatty Liver Disease Using Bioinformatics Analysis

Mahmoudi

Butler

Jamialahmadi

et al. 2021

BioMed Research International

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Background. Nonalcoholic fatty liver disease (NAFLD) is a prevalent form of liver damage, affecting ~25% of the global population. NAFLD comprises a spectrum of liver pathologies, from hepatic steatosis to nonalcoholic steatohepatitis (NASH), and may progress to liver fibrosis and cirrhosis. The presence of NAFLD correlates with metabolic disorders such as hyperlipidemia, obesity, blood hypertension, cardiovascular, and insulin resistance. Fenofibrate is an agonist drug for peroxisome proliferator-activated receptor alpha (PPARα), used principally for treatment of hyperlipidemia. However, fenofibrate has recently been investigated in clinical trials for treatment of other metabolic disorders such as diabetes, cardiovascular disease, and NAFLD. The evidence to date indicates that fenofibrate could improve NAFLD. While PPARα is considered to be the main target of fenofibrate, fenofibrate may exert its effect through impact on other genes and pathways thereby alleviating, and possibly reversing, NAFLD. In this study, using bioinformatics tools and gene-drug, gene-diseases databases, we sought to explore possible targets, interactions, and pathways involved in fenofibrate and NAFLD. Methods. We first determined significant protein interactions with fenofibrate in the STITCH database with high confidence (0.7). Next, we investigated the identified proteins on curated targets in two databases, including the DisGeNET and DISEASES databases, to determine their association with NAFLD. We finally constructed a Venn diagram for these two collections (curated genes-NAFLD and fenofibrate-STITCH) to uncover possible primary targets of fenofibrate. Then, Gene Ontology (GO) and KEGG were analyzed to detect the significantly involved targets in molecular function, biological process, cellular component, and biological pathways. A P value < 0.01 was considered the cut-off criterion. We also estimated the specificity of targets with NAFLD by investigating them in disease-gene associations (STRING) and EnrichR (DisGeNET). Finally, we verified our findings in the scientific literature. Results. We constructed two collections, one with 80 protein-drug interactions and the other with 95 genes associated with NAFLD. Using the Venn diagram, we identified 11 significant targets including LEP, SIRT1, ADIPOQ, PPARA, SREBF1, LDLR, GSTP1, VLDLR, SCARB1, MMP1, and APOC3 and then evaluated their biological pathways. Based on Gene Ontology, most of the targets are involved in lipid metabolism, and KEGG enrichment pathways showed the PPAR signaling pathway, AMPK signaling pathway, and NAFLD as the most significant pathways. The interrogation of those targets on authentic disease databases showed they were more specific to both steatosis and steatohepatitis liver injury than to any other diseases in these databases. Finally, we identified three significant genes, APOC3, PPARA, and SREBF1, that showed robust drug interaction with fenofibrate. Conclusion. Fenofibrate may exert its effect directly or indirectly, via modulation of several key targets and pathways, in the treatment of NAFLD.

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“…[5][6][7] Several studies have investigated the association between gene polymorphisms and NAFLD. [8][9][10][11] Acetaldehyde dehydrogenase 2 (ALDH2) is an enzyme involved in redox homeostasis and hepatic ethanol metabolism. 12,13 The rs671 polymorphism (also named Glu504Lys) has been the most commonly studied.…”

Section: Introductionmentioning

confidence: 99%

The Association and Interaction of Aldehyde Dehydrogenase 2 Polymorphisms with Food Group Intake and Probability of Having Non-Alcoholic Fatty Liver Disease

Hao

Zeng

2020

DMSO

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Purpose This study investigated the association between the aldehyde dehydrogenase 2 (ALDH2) rs671 polymorphism, food group intake, and the probability of having non-alcoholic fatty liver disease (NAFLD) in a Chinese population. Patients and Methods A total of 3506 adults were enrolled in this study, and all underwent physical examinations and genotyping of polymorphisms with polymerase chain reaction. Participants filled out a dietary questionnaire that was used to assess the frequency and quantity of food consumption. Results We found that milk groups were associated with a lower probability of developing NAFLD. On the contrary, meat and salted and smoked foods were associated with a higher probability of NAFLD. However, the influences of salted and smoked foods and fresh fruit and vegetables on NAFLD were obviously different in the two genotype groups. Salted and smoked foods intake was a factor associated with a higher probability of having NAFLD or nonalcoholic steatohepatitis (NASH) in the A genotype group, but there was no effect in the G genotype group. Moreover, eating salted and smoked foods several times per week was associated with a higher probability of having NAFLD than seldom consuming them. Consumption of fresh fruit and vegetables was not a factor influencing the probability of having NAFLD in the A genotype group, and there was no effect in the G genotype group. Further analysis of the interaction indicated that the GA +AA genotype showed an interaction with fresh fruit and vegetables and salted and smoked foods. Moreover, it was not obvious that meat intake increased the probability of having NAFLD or NASH among different genotypes. Conclusion Our results indicate that ALDH2 rs671 GA and AA genotypes are factors associated with increased probability of NAFLD among Chinese subjects. This could stimulate the development of novel approaches for preventing NAFLD.

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Association between ADIPOQ G276T and C11377G polymorphisms and the risk of non‐alcoholic fatty liver disease: An updated meta‐analysis

Cited by 11 publications

References 31 publications

Associations Among Methylene Tetrahydrofolate Reductase rs1801133 C677T Gene Variant, Food Groups, and Non-alcoholic Fatty Liver Disease Risk in the Chinese Population

Associations Among Methylene Tetrahydrofolate Reductase rs1801133 C677T Gene Variant, Food Groups, and Non-alcoholic Fatty Liver Disease Risk in the Chinese Population

Target Deconvolution of Fenofibrate in Nonalcoholic Fatty Liver Disease Using Bioinformatics Analysis

The Association and Interaction of Aldehyde Dehydrogenase 2 Polymorphisms with Food Group Intake and Probability of Having Non-Alcoholic Fatty Liver Disease

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